Assessment of long-term effects of nanoparticles in a microcarrier cell culture system.
Nano-sized materials could find multiple applications in medical diagnosis and therapy. One main concern is that engineered nanoparticles, similar to combustion-derived nanoparticles, may cause adverse effects on human health by accumulation of entire particles or their degradation products. Chronic cytotoxicity must therefore be evaluated. In order to perform chronic cytotoxicity testing of plain polystyrene nanoparticles on the endothelial cell line EAhy 926, we established a microcarrier cell culture system for anchorage-dependent cells (BioLevitator(TM)). Cells were cultured for four weeks and exposed to doses, which were not cytotoxic upon 24 hours of exposure. For comparison, these particles were also studied in regularly sub-cultured cells, a method that has traditionally been used to assess chronic cellular effects. Culturing on basal membrane coated microcarriers produced very high cell densities. Fluorescent particles were mainly localized in the lysosomes of the exposed cells. After four weeks of exposure, the number of cells exposed to 20 nm polystyrene particles decreased by 60% as compared to untreated controls. When tested in sub-cultured cells, the same particles decreased cell numbers to 80% of the untreated controls. Dose-dependent decreases in cell numbers were also noted after exposure of microcarrier cultured cells to 50 nm short multi-walled carbon nanotubes. Our findings support that necrosis, but not apoptosis, contributed to cell death of the exposed cells in the microcarrier culture system. In conclusion, the established microcarrier model appears to be more sensitive for the identification of cellular effects upon prolonged and repeated exposure to nanoparticles than traditional sub-culturing.


Fetal topographical anatomy of the pancreatic head and duodenum with special reference to courses of the pancreaticoduodenal arteries.
The purpose of this study is to provide better understanding as to how the "double" vascular arcades, in contrast to other intestinal marginal vessels, develop along the right margin of the pancreatic head. In human fetuses between 8-30 weeks, we described the topographical anatomy of the vessels, bile duct, duodenum as well as the ventral and dorsal primordia of the pancreatic head with an aid of pancreatic polypeptide immunohisto-chemistry. The contents of the hepatoduodenal ligament crossed the superior side of the pylorus. Moreover, the right hepatic artery originating from the superior mesenteric artery ran along the superior aspect of the pancreatic head. An arterial arcade, corresponding to the posterior pancreaticoduodenal arteries, encircled the superior part of the pancreatic head, whereas another arcade, corresponding to the anterior pancreaticoduodenal arteries, surrounded the inferior part. The dorsal promordium of the pancreas surrounded and/or mixed the ventral primordium at 13-16 weeks. Thus, both arterial arcades were likely to attach to the dorsal primordium. The fetal anatomy of the pancreaticoduodenal vascular arcades as well as that of the hepatoduodenal ligament were quite different from adults in topographical relations. Thus, in the stage later than 30 weeks, further rotation of the duodenum along a horizontal axis seemed to be required to move the pylorus posterosuperiorly and to reflect the superior surface of the pancreatic head posteriorly. However, to change the topographical anatomy of the superior and inferior arterial arcades into the final position, re-arrangement of the pancreatic parenchyma might be necessary in the head.


The Rsm (Csr) post-transcriptional regulatory pathway coordinately controls multiple CRISPR-Cas immune systems.
CRISPR-Cas systems provide bacteria with adaptive immunity against phages and plasmids; however, pathways regulating their activity are not well defined. We recently developed a high-throughput genome-wide method (SorTn-seq) and used this to uncover CRISPR-Cas regulators. Here, we demonstrate that the widespread Rsm/Csr pathway regulates the expression of multiple CRISPR-Cas systems in Serratia (type I-E, I-F and III-A). The main pathway component, RsmA (CsrA), is an RNA-binding post-transcriptional regulator of carbon utilisation, virulence and motility. RsmA binds cas mRNAs and suppresses type I and III CRISPR-Cas interference in addition to adaptation by type I systems. Coregulation of CRISPR-Cas and flagella by the Rsm pathway allows modulation of adaptive immunity when changes in receptor availability would alter susceptibility to flagella-tropic phages. Furthermore, we show that Rsm controls CRISPR-Cas in other genera, suggesting conservation of this regulatory strategy. Finally, we identify genes encoding RsmA homologues in phages, which have the potential to manipulate the physiology of host bacteria and might provide an anti-CRISPR activity.


Symptoms and musculoskeletal diseases in hospital nurses and in a group of university employees: a cross-sectional study.
Most studies have shown that nurses have a higher risk of developing musculoskeletal symptoms compared with other occupational groups. A cross-sectional study was performed to gain more insight into the prevalence rates of musculoskeletal disorders (MSDs) in nurses. The presence of musculoskeletal symptoms was revealed by personal interviews in a sample of 177 hospital nurses and in a reference group of 185 university employees. Musculoskeletal diseases were based on radiological examinations in all subjects. Lower back pain (61% vs 42.2%) was the most frequently reported symptom, followed by neck pain (48.6% vs 38.4%) and shoulder pain (36.7% vs 25.9%), with a significantly higher prevalence in nurses. Women had about a 2-fold risk of upper limb region and neck pain compared with men. The most common abnormal findings on radiological examinations were disc herniations (n = 40). Nurses showed a significantly higher risk of MSDs. Prevalence rates in nurses increased significantly with age. Musculoskeletal symptoms were also common in university employees. This suggests the need for effective intervention strategies involving workers' active participation, in order to improve the process and organization of work and promote a positive psychosocial work environment.


[Observation on therapeutic effect of Rhubarb and sanchi powder in treating patients with hemorrhagic fever in nephrotic syndrome complicated with digestive tract bleeding].
To observe the therapeutic effect of rhubarb and Sanchi Powder (RSP) in treating patients with hemorrhagic fever in nephrotic syndrome (NS) complicated with digestive tract bleeding. Sixty patients clinically diagnosed as hemorrhagic fever in NS complicated with digestive tract bleeding were randomized into 2 groups. Fine ground rhubarb (3g) and SP (2g) were given orally to the patients in the treated group 3 - 4 times daily. Dicynonum (2g) was given by intravenously dripping to the patients in the control group. In the treated group, 17 patients were cured, 5 markedly effective and 6 effective, with the markedly effective rate of 70.97% and the total effective rate of 90.32%. The corresponding number in the control group was 10, 3, 6, 44.83% and 65.52%, respectively, significant difference was shown in comparison between the two groups (P < 0.05 or P < 0.01). The average hemostatic time was (2.32 +/- 0.82) h, the platelet count was (8.84 +/- 1.13) x 10(9) /L, and the platelet aggregation rate was obviously improved in the treated group, which were significantly different to those in the control group [(4.15 +/- 0.69) h, (6.22 +/- 0.89) x 10(9)/L, respectively, P<0.01). RSP has the action of promoting vasoconstriction, shortening the bleeding time and blood arresting, it can increase the platelet count and improve the platelet aggregation.


[Public spending on health and population health in Algeria: an econometric analysis].
Objective: The objective of this study was to estimate the impact of public spending on health, among other determinants of health, on the health of the population in Algeria, using life expectancy (men and women) and infant mortality rates as indicators of health status. Methods: We conducted a longitudinal study over the period from 1974 to 2010 using the ARDL (Autoregressive Distributed Lags) approach to co-integration to estimate the short-term and long-term relationship. Results: Public spending on health has a positive, but not statistically significant impact, in the long and short term, on life expectancy (men and women). However, public spending significantly reduces the infant mortality rate. The long-term impact of the number of hospital beds is significant for the life expectancy of men, but not for women and infant mortality, but is significant for all indicators in the short-term relationship. The most important variables in improving the health of the population are real GDP per capita and fertility rate.


Evidence-based toxicology: "sound science" in new disguise.
The "evidence-based toxicology" proposed by Guzelian et al. departs radically from state-of-the-art toxicology by claiming that risks for humans can only be determined on the basis of human evidence. Just like the previous proposal of "sound science," "evidence-based toxicology" poses a heavy burden of proof on any effort to control exposures in order to reduce health risks to those exposed. The alleged connection between "evidence-based toxicology" and evidence-based medicine is misconceived, since the strict criteria for use of scientific data in evidence-based medicine concerns proof of therapeutic effects, while in "evidence-based toxicology" these criteria are applied to proof of harmful effects. The slogans "sound science" and "evidence-based toxicology" have both been put forward by persons with a history of extensive involvement with the tobacco industry.


Prevalence analysis of de novo hepatic steatosis following pylorus-preserving pancreaticoduodenectomy.
Prevalence of hepatic steatosis following pylorus-preserving pancreaticoduodenectomy (PPPD) is high. This study intended to reveal the prevalence and patterns of de novo hepatic steatosis following PPPD. We investigated postoperative de novo hepatic steatosis following PPPD (n = 101) with a control group of bile duct resection (BDR) (n = 54). At postoperative 1 year, hepatic steatosis occurred in 21 of 82 patients (25.6%) of PPPD group and in 2 of 47 patients (4.3%) of BDR group (p = 0.001). Thereafter, at 2 to 5 years, a high prevalence of hepatic steatosis persisted in the PPPD group, but no further occurrence developed in BDR group. Once steatosis developed, it persisted until the end of the study period or patient death. Five-year cumulative incidence of hepatic steatosis was 26.7% in the PPPD group and 3.7% in BDR group (p < 0.001). Univariate analyses showed that patient sex, age, body mass index, blood lipid profile, recurrence of tumor, and diabetes did not have significant influence on the development of hepatic steatosis following PPPD. De novo hepatic steatosis may develop in a not negligible proportion of patients undergone PPPD. Multicenter studies with a high number of patients are needed to elucidate its pathogenesis and to find effective treatment for pancreaticoduodenectomy-associated hepatic steatosis.


Immunomodulatory Nanosystems: Advanced Delivery Tools for Treating Chronic Wounds.
The increasingly aging society led to a rise in the prevalence of chronic wounds (CWs), posing a significant burden to public health on a global scale. One of the key features of CWs is the presence of a maladjusted immune microenvironment characterized by persistent and excessive (hyper)inflammation. A variety of immunomodulatory therapies have been proposed to address this condition. Yet, to date, current delivery systems for immunomodulatory therapy remain inadequate and lack efficiency. This highlights the need for new therapeutic delivery systems, such as nanosystems, to manage the pathological inflammatory imbalance and, ultimately, improve the treatment outcomes of CWs. While a plethora of immunomodulatory nanosystems modifying the immune microenvironment of CWs have shown promising therapeutic effects, the literature on the intersection of immunomodulatory nanosystems and CWs remains relatively scarce. Therefore, this review aims to provide a comprehensive overview of the pathogenesis and characteristics of the immune microenvironment in CWs, discuss important advancements in our understanding of CW healing, and delineate the versatility and applicability of immunomodulatory nanosystems-based therapies in the therapeutic management of CWs. In addition, we herein also shed light on the main challenges and future perspectives in this rapidly evolving research field.


The intestinal crypt, a prototype stem cell compartment.
Due to its intense self-renewal kinetics and its simple repetitive architecture, the intestinal epithelium has become a prime model for studying adult stem cells in health and disease. Transgenic mouse models allow in vivo visualization and genetic lineage tracing of individual intestinal stem cells and their offspring. Fluorescently marked stem cells can be isolated for molecular analyses or can be cultured to build ever-expanding "mini-guts" in vitro. These studies are filling in the outlines of a robust homeostatic self-renewal process that defies some of the classical definitions of stem cell behavior, such as asymmetric division, quiescence, and exhaustion.


Non-Vesicular Lipid Transport Machinery in Leishmania donovani: Functional Implications in Host-Parasite Interaction.
Eukaryotic cells have distinct membrane-enclosed organelles, each with a unique biochemical signature and specialized function. The unique identity of each organelle is greatly governed by the asymmetric distribution and regulated intracellular movement of two important biomolecules, lipids, and proteins. Non-vesicular lipid transport mediated by lipid-transfer proteins (LTPs) plays essential roles in intra-cellular lipid trafficking and cellular lipid homeostasis, while vesicular transport regulates protein trafficking. A comparative analysis of non-vesicular lipid transport machinery in protists could enhance our understanding of parasitism and basis of eukaryotic evolution. Leishmania donovani, the trypanosomatid parasite, greatly depends on receptor-ligand mediated signalling pathways for cellular differentiation, nutrient uptake, secretion of virulence factors, and pathogenesis. Lipids, despite being important signalling molecules, have intracellular transport mechanisms that are largely unexplored in L. donovani. We have identified a repertoire of sixteen (16) potential lipid transfer protein (LTP) homologs based on a domain-based search on TriTrypDB coupled with bioinformatics analyses, which signifies the presence of well-organized lipid transport machinery in this parasite. We emphasized here their evolutionary uniqueness and conservation and discussed their potential implications for parasite biology with regards to future therapeutic targets against visceral leishmaniasis.


Being like everybody else: the personal meanings of being a prosthesis user.
This study sought to gain an understanding of the lived experience of prosthesis use for amputees and people with congenital limb deficiency. The primary data were transcripts derived from semi-structured interviews and the documentary analysis of two e-mail discussion groups for prosthesis users. This data was subject to an interpretative phenomenological analysis. Three recurrent themes are presented. These are: Dreams and Realities: Enabling Prostheses; Being Like Everybody Else: The Meanings of Cosmesis; and Passing, Telling and Getting Away With It: Disguising Prosthesis Use. It is argued that prostheses have a number of deeply personal meanings for participants, which revolve around what people can practically achieve with a prosthetic limb, and the management of personal information and identity. The research outcomes suggest that it is important for health professionals involved in prosthesis users' medical care and personal welfare to facilitate the maintenance of these patients valued identities and the self management of their disability status.


Relationship of heart rate turbulence, heart rate variability and the number of ventricular premature beats in patients with mitral valve prolapse and non-significant regurgitation.
Cardiac arrhythmia is frequently detected in patients with mitral valve prolapse (MVP) and improper autonomic tone is considered the etiology. Heart rate turbulence (HRT) and heart rate variability (HRV) are methods assessed for autonomic dysfunction. To evaluate whether the number of ventricular premature contractions (VPCs) is influenced by HRT or HRV in patients with MVP. Holter monitoring for the number of VPCs and correlation analysis with HRT and HRV was performed. There were 31% and 3% with abnormal turbulence onset (TO) and turbulence slope (TS) values in totally 68 patients. No significant correlation is found between the number of VPCs and HRT, HRV parameters. In analysis the relationship between HRT and HRV parameters, TS has higher correlation with HRV than TO values, particular in time-domain.


[Extracellular matrix as a microbial virulence factor in the development of human diseases].
Extracellular polymers which build a biofilm matrix possess a complicated structure, where the polysaccharide fraction, composed of homo- or heteropolysaccharides, is the largest. Other important components are proteins, eDNA, glycoproteins and lipids. The matrix has a protective function against the surrounding environment, plays a role in biofilm formation and maturation processes, stabilizes the biofilm structure, and also is a source of nutrients and water for the cells. It is noteworthy that the biofilm matrix is a virulence factor and plays an important role in the pathogenesis of many human diseases. Pseudomonas aeruginosa growing in the lungs of patients with cystic fibrosis produces three major exopolysaccharides (Pel, Psl and alginate) and synthesizes numerous proteins such as lectins and enzymes, e.g. PasP, chitinase, aminopeptidase, and protease IV, which facilitate the tissue colonization. Extracellular polymers play a significant role in the course of caries, which is associated with the development of multi-species biofilm on the teeth surface. The structure of the matrix surrounding that biofilm is complicated--different for each patient. The components of the matrix are constantly changing depending on the environmental conditions, e.g. the presence of sucrose affects the synthesis of mutan and dextran. Infections associated with biofilm formation on implants pose significant medical and economic problems. The main components of the matrices are saccharides (e.g., PIA, EC-TA), as well as surface and extracellular proteins. Studies on the matrix structure and the factors regulating its synthesis are necessary to develop techniques for biofilm eradication and better control of biofilm-related infections.


Investigating Parallel Analysis in the Context of Missing Data: A Simulation Study Comparing Six Missing Data Methods.
Exploratory factor analysis is a statistical method commonly used in psychological research to investigate latent variables and to develop questionnaires. Although such self-report questionnaires are prone to missing values, there is not much literature on this topic with regard to exploratory factor analysis-and especially the process of factor retention. Determining the correct number of factors is crucial for the analysis, yet little is known about how to deal with missingness in this process. Therefore, in a simulation study, six missing data methods (an expectation-maximization algorithm, predictive mean matching, Bayesian regression, random forest imputation, complete case analysis, and pairwise complete observations) were compared with respect to the accuracy of the parallel analysis chosen as retention criterion. Data were simulated for correlated and uncorrelated factor structures with two, four, or six factors; 12, 24, or 48 variables; 250, 500, or 1,000 observations and three different missing data mechanisms. Two different procedures combining multiply imputed data sets were tested. The results showed that no missing data method was always superior, yet random forest imputation performed best for the majority of conditions-in particular when parallel analysis was applied to the averaged correlation matrix rather than to each imputed data set separately. Complete case analysis and pairwise complete observations were often inferior to multiple imputation.


[The value of routine lymphadenectomy in radical Wertheim hysterectomies (author's transl)].
In 1959 Rauscher and Spurny questioned the advantages of routine lymphadenectomy in radical Wertheim operations compared to selective lymphadenectomies. Our present review disagrees with the above mentioned doubts. Rauscher and Spurny base their results on clinical staging of cancer of the cervix in cases from 1947 to 1950, and in cases from 1950 to 1953. Our results are quite different in two groups of patients from the years 1946 to 1949 and 1951 to 1953 with the staging done by histological methods. In the later period of 1965-1969 the results were further improved, probably due to the extent of the lymphadenectomy. The routine lymphadenectomy showed improved results not only in all cases but also in the cases with carcinoma of the lymph nodes.


Social justice as a framework for professional nursing.
A persistent connection exists between health disparity and societal inequality. Since more research is designed to document, rather than alter, those trends, nurses are called on to reinvest in a social justice agenda. An educational focus on social justice is necessary to prepare future nurses to address health concerns related to how societies are structured. This article reports on how social justice was used as a framework to teach concepts related to professional nursing. The course structure is described, a focus on how the course content was taught is outlined, and conclusions are drawn. Linking content on social justice to professional nursing is important because research indicates that, if societal relationships are more equal, population health indicators between diverse groups become more stable nationally and globally.


Associations of Long-Term Visit-to-Visit Blood Pressure Variability With Subclinical Kidney Damage and Albuminuria in Adulthood: a 30-Year Prospective Cohort Study.
Recent evidence indicates that long-term visit-to-visit blood pressure variability (BPV) may be associated with risk of cardiovascular disease. We, therefore, aimed to determine the potential associations of long-term BPV from childhood to middle age with subclinical kidney damage (SKD) and albuminuria in adulthood. Using data from the ongoing cohort of Hanzhong Adolescent Hypertension study, which recruited children and adolescents aged 6 to 18 years at baseline, we assessed BPV by SD and average real variability (ARV) for 30 years (6 visits). Presence of SKD was defined as estimated glomerular filtration rate between 30 and 60 mL/min per 1.73 m2 or elevated urinary albumin-to creatinine ratio at least 30 mg/g. Albuminuria was defined as urinary albumin-to creatinine ratio ≥30 mg/g. During 30 years of follow-up, of the 1771 participants, 204 SKD events occurred. After adjustment for demographic, clinical characteristics, and mean BP during 30 years, higher SDSBP , ARVSBP , SDDBP , ARVDBP , SDMAP , ARVMAP , and ARVPP were significantly associated with higher risk of SKD. When we used cumulative exposure to BP from childhood to adulthood instead of mean BP as adjustment factors, results were similar. In addition, greater long-term BPV was also associated with the risk of albuminuria. Long-term BPV from childhood to middle age was associated with higher risk of SKD and albuminuria in adulthood, independent of mean BP or cumulative exposure to BP during follow-up. Identifying long-term BPV from early age may assist in predicting kidney disease and cardiovascular disease in later life.


Assessing Adherence to Multi-Modal Oura Ring Wearables From COVID-19 Detection Among Healthcare Workers.
Background Identifying early signs of a SARS-CoV-2 infection in healthcare workers could be a critical tool in reducing disease transmission. To provide this information, both daily symptom surveys and wearable device monitoring could have utility, assuming there is a sufficiently high level of participant adherence. Purpose The aim of this study is to evaluate adherence to a daily symptom survey and a wearable device (Oura Ring) among healthcare professionals (attending physicians and other clinical staff) and trainees (residents and medical students) in a hospital setting during the early stages of the COVID-19 pandemic. Methods In this mixed-methods observational study, the data were a subset (N=91) of those collected as part of the larger TemPredict Study. Demographic data analyses were conducted with descriptive statistics. Participant adherence to the wearable device protocol was reported as the percentage of days that sleep was recorded, and adherence to the daily survey was reported as the percentage of days with submitted surveys. Comparisons for the primary (wearable and survey adherence of groups) and secondary (adherence patterns among subgroups) outcomes were conducted using descriptive statistics, two-tailed independent t-tests, and Welch's ANOVA with post hoc analysis using Games-Howell. Results Wearable device adherence was significantly higher than the daily symptom survey adherence for most participants. Overall, participants were highly adherent to the wearable device, wearing the device an average of 87.8 ± 11.6% of study nights compared to survey submission, showing an average of 63.8 ± 27.4% of study days. In subgroup analysis, we found that healthcare professionals (HCPs) and medical students had the highest adherence to wearing the wearable device, while medical residents had lower adherence in both wearable adherence and daily symptom survey adherence. Conclusions These results indicated high participant adherence to wearable devices to monitor for impending infection in the course of a research study conducted as part of clinical practice. Subgroup analysis indicated HCPs and medical students maintained high adherence, but residents' adherence was lower, which is likely multifactorial, with differences in work demands and stress contributing to the findings. These results can guide the development of adherence strategies for a wearable device to increase the quality of data collection and assist in disease detection in this and future pandemics.


Type of LDLR mutation and the pharmacogenetics of familial hypercholesterolemia treatment.
Familial hypercholesterolemia (FH) is an autosomal dominant disease mainly caused by mutations in the low-density lipoprotein receptor (LDLR) gene. FH patients present a wide variability regarding response to drugs and they are usually undertreated. Here, we review studies that evaluated the association between the type of LDLR mutation and the response to lipid-lowering therapy. The main findings were that patients with a null LDLR mutation had: higher baseline LDL-C, higher LDL-C after drug therapy, lower proportion of patients within the LDL-C target value and higher frequencies of CVD. Thus, we conclude that FH patients harboring a null mutation have a trend to an increased risk, even if diagnosis is early established and lipid-lowering treatment instituted. It is suggested that these individuals may benefit from the use of newly approved lipid-lowering agents.


Synthesis of TiO2-Au composites by titania-nanorod-assisted generation of gold nanoparticles at aqueous/nonpolar interfaces.
Hydrophobically coated anatase TiO(2) nanorods can assist the reduction of AuCl(4) (-)ions at aqueous/nonpolar solvent interfaces, which results in the generation of organic-soluble Au nanoparticles with tunable size in the absence of any metal ligands and/or phase-transfer agents. The titania-nanorod-driven modulation of interfacial energy and catalysis of gold nucleation provide straightforward access to nanocomposite solutions of TiO(2)-stabilized Au nanoparticles. Among colloidal approaches, this method represents a unique tool for the surfactantless, large-scale preparation of nanostructured semiconductor-metal hybrid systems with relevant technological potential in catalysis, photocatalysis, and charge-storage processes.


Chronic Pain: Structural and Functional Changes in Brain Structures and Associated Negative Affective States.
Chronic pain is a condition in which pain progresses from an acute to chronic state and persists beyond the healing process. Chronic pain impairs function and decreases patients' quality of life. In recent years, efforts have been made to deepen our understanding of chronic pain and to develop better treatments to alleviate chronic pain. In this review, we summarize the results of previous studies, focusing on the mechanisms underlying chronic pain development and the identification of neural areas related to chronic pain. We review the association between chronic pain and negative affective states. Further, we describe the structural and functional changes in brain structures that accompany the chronification of pain and discuss various neurotransmitter families involved. Our review aims to provide guidance for the development of future therapeutic approaches that could be used in the management of chronic pain.


Increasing nausea and vomiting of pregnancy is associated with sex-dependent differences in early childhood growth: the GUSTO mother-offspring cohort study.
Nausea and vomiting of pregnancy (NVP) is common and underlying mechanisms are poorly understood. Longer-term offspring outcomes are also not well documented. This study aimed to determine if NVP, even in milder forms, is associated with adverse pregnancy and childhood growth outcomes. In the GUSTO prospective mother-offspring cohort, women with singleton pregnancies (n = 1172) recruited in first trimester responded to interviewer-administered questions at 26-28 weeks' gestation about earlier episodes of NVP since becoming pregnant. Pregnancy outcomes were obtained from medical records. Offspring height and weight measured at 15 time-points between birth to 72 months (m) were standardised for age and sex. 58.5% (n = 686) reported mild-moderate vomiting (mNVP), 10.5% (n = 123) severe vomiting (sNVP) and 5.7% (n = 67) severe vomiting with hospitalisation (shNVP). There was no difference in odds of gestational diabetes, hypertensive disorders of pregnancy, labour induction or caesarean section after adjustment for covariates. sNVP was associated with late preterm delivery [34+ 0-36+ 6 weeks', adjusted OR = 3.04 (95% CI 1.39,6.68)], without increased odds of neonatal unit admission. Compared with no NVP, boys born to mothers with sNVP were longer at birth [adjusted β = 0.38 standard deviations (SDs) (95% CI 0.02,0.73)], remained taller [0.64 SDs (0.23,1.04) at 72 m] and heavier [0.57 SDs (0.05,1.08) at 60 m] without differences in BMI. Conversely, girls born to mothers with shNVP were lighter from 48 m [- 0.52 SDs (- 1.00, - 0.03)] onwards with lower BMI [- 0.61 SDs (- 1.12,-0.09)]. Conditional growth modelling revealed significant sex-divergence in weight-gain at birth-3 m, 6-9 m and 4-5 years. Severe NVP was associated with late preterm delivery, and both mild-moderate and severe NVP associated with sex-dependent differences in early childhood growth. Boys whose mothers had NVP were taller and heavier from birth with faster growth in the first year, whereas, girls had poorer weight gain and were lighter by 48 m. As even milder severities of NVP could have long-term impact on offspring growth, further research is needed to determine mechanisms involved and implications on future health. Clinicaltrials.gov identifier NCT01174875 .


Inhibition of peroxynitrite dependent tyrosine nitration by hydroxycinnamates: nitration or electron donation?
Peroxynitrite is a cytotoxic species generated by the reaction between superoxide and nitric oxide. In this study the ability of hydroxycinnamate antioxidants to decrease peroxynitrite-mediated nitration of tyrosine was investigated. The results obtained show that all compounds were able to inhibit nitration of tyrosine. The potency of inhibitory activity was in the order; caffeic acid > or = chlorogenic acid > or = ferulic acid > p-coumaric acid > ocoumaric acid > m-coumaric acid. Trolox, which was included in the study for comparative purposes, had an activity between that of ferulic acid and p-coumaric acid. The data obtained suggest that hydroxycinnamates can act by one of two possible mechanisms: preferential nitration for monophenolates and electron donation by catecholates.


FABP7 upregulation induces a neurotoxic phenotype in astrocytes.
Fatty acid binding proteins (FABPs) are key regulators of lipid metabolism, energy homeostasis, and inflammation. They participate in fatty acid metabolism by regulating their uptake, transport, and availability of ligands to nuclear receptors. In the adult brain, FABP7 is especially abundant in astrocytes that are rich in cytoplasmic granules originated from damaged mitochondria. Mitochondrial dysfunction and oxidative stress have been implicated in the neurodegenerative process observed in amyotrophic lateral sclerosis (ALS), either as a primary cause or as a secondary component of the pathogenic process. Here we investigated the expression of FABP7 in animal models of human superoxide dismutase 1 (hSOD1)-linked ALS. In the spinal cord of symptomatic mutant hSOD1-expressing mice, FABP7 is upregulated in gray matter astrocytes. Using a coculture model, we examined the effect of increased FABP7 expression in astrocyte-motor neuron interaction. Our data show that FABP7 overexpression directly promotes an NF-κB-driven pro-inflammatory response in nontransgenic astrocytes that ultimately is detrimental for motor neuron survival. Addition of trophic factors, capable of supporting motor neuron survival in pure cultures, did not prevent motor neuron loss in cocultures with FABP7 overexpressing astrocytes. In addition, astrocyte cultures obtained from symptomatic hSOD1-expressing mice display upregulated FABP7 expression. Silencing endogenous FABP7 in these cultures decreases the expression of inflammatory markers and their toxicity toward cocultured motor neurons. Our results identify a key role of FABP7 in the regulation of the inflammatory response in astrocytes and identify FABP7 as a potential therapeutic target to prevent astrocyte-mediated motor neuron toxicity in ALS.


Measures to support informal care for the older adults in Kazakhstan: a review of the current status.
The demand for informal caregivers to support the older adults has grown worldwide in recent decades. However, informal caregivers themselves require support. This article aims to examine existing support measures for caregivers of the older adults in the Republic of Kazakhstan. Relevant articles and grey literature were identified through manual searches on Google and Google Scholar, as well as electronic searches using indexed databases like PubMed, Web of Science, and Scopus. Moreover, the reference lists of identified sources and government ministry websites were meticulously scrutinized. This review highlights the scarcity of research on caregiver support measures in Kazakhstan, supported by the lack of peer-reviewed articles on this subject. A comprehensive analysis of the literature shows that in Kazakhstan's legislative framework, "caregivers" exclusively refers to individuals providing care for a first-degree disability. The responsibility of caring for older adults parents lies with able-bodied children. However, there is a lack of registration and assessment procedures to evaluate the burden and quality of life of caregivers. As a result, the medical and social support provided to caregivers is standardized, failing to adequately address their unique needs and requirements. The analysis of current support measures for informal caregivers highlights the need to develop support mechanisms and recognize individuals providing informal care as key figures in the long-term care system.


Interleukin 1 induction of the c-jun promoter.
Interleukin 1 (IL-1) induces pleiotropic effects in many cell types during inflammation and immunity. We have recently shown how the IL-1 signal is transmitted to the nucleus: In T cells and in pituitary cells, IL-1 induced genes via activation of the nuclear factor AP-1. We now demonstrate how IL-1 activates the AP-1 factor in liver cells, which are a major target for IL-1 during the acute phase response in vivo. IL-1 induced gene transcription of both AP-1 components, c-jun and c-fos. IL-1 also increased the stability of c-jun mRNA. We define two enhancer sites in the jun promoter that are required for induction by IL-1. Although the binding sites share some similarity with the AP-1 binding site, the nuclear factors binding the jun motifs are not composed of Jun or Fos proteins. Thus these data identify two binding proteins that serve as one of the first nuclear targets for IL-1 signal transduction.


Asynchrony between position and motion signals in the saccadic system.
The influence of position and motion signals on saccades was studied in two dimensions (2D) using a double step-ramp paradigm. We showed the presence of a predictive component in 2D catch-up saccade programming that is based on motion signals and influences both saccade amplitude and orientation. Interestingly, a significant proportion of catch-up saccades was characterized by a large curvature or a sudden change of direction in midflight for large values of retinal slip. For these saccades, a quantitative analysis showed that their trajectory could be explained by an asynchrony between position and motion signals in saccade programming. When the saccade trajectory was not straight, position error was always available first and influenced the initial orientation of the saccade, whereas retinal slip determined the final orientation. This new paradigm could be used in electrophysiological experiments, where it should prove to be very useful to study position and motion pathways separately in catch-up saccades.


Survey of opioid tapering practices of pediatric healthcare providers: A national perspective.
The purpose of this study was to describe the current opioid tapering practice. Cross-sectional, online, survey research. Pediatric healthcare providers from a national sample of practicing nurse practitioners, physician assistants, and physicians who participate in five different pediatric pain and/or palliative care list serves. One hundred four participants responded to the survey. The respondents were predominantly physicians (n = 58, 62 percent). The majority of respondents worked in an academic children's medical center (n = 50, 52 percent). The average number of years in pediatric practice was 16 (mean = 16.33, range of 0-45 years). Of the 104 respondents, only 22 (27 percent) had a written protocol for opioid tapering. Use of expert consultants such as pharmacists or pediatric pain management teams varied. The majority of respondents (n = 46, 44 percent) seldom or never consult a pharmacist. Only 22 percent (n = 17) almost always or always consult a pediatric pain team. There was a wide range of personal tapering rate preferences. This study provided a baseline assessment of pediatric opioid tapering practices by pediatric healthcare providers. Results revealed a marked variation in practice patterns that may indicate deficits in the assessment and management of opioid withdrawal in children. The need for the development of assessment-based opioid tapering guidelines for the pediatric population is long overdue.


Genetic diversity of integrase (IN) sequences in antiretroviral treatment-naive and treatment-experienced HIV type 2 patients.
Two potent integrase inhibitors (IN-Is), raltegravir (RAL, MK-0518) and elvitegravir (EGV, GS-9137), have been shown to be potent inhibitors for HIV-1 and resistance mutations have been identified in HIV-1 clinical trials. In this study, sequences from 11 HIV-2 patients were examined for IN polymorphisms. The primary mutations associated with RAL and EGV resistance were not detected despite the genetic variability among clinical isolates. Our study provides basic information on genotypic susceptibility of HIV-2 to RAL and EGV and supports the suggestion that RAL and EGV could be considered as a new therapeutic option for treating HIV-2-infected patients.


Employing Deep Learning Model to Evaluate Speech Information in Acoustic Simulations of Auditory Implants.
Acoustic simulations have played a prominent role in the development of speech processing and sound coding strategies for auditory neural implant devices. Traditionally evaluated using human subjects, acoustic simulations have been used to model the impact of implant signal processing as well as individual anatomy/physiology on speech perception. However, human subject testing is time-consuming, costly, and subject to individual variability. In this study, we propose a novel approach to perform simulations of auditory implants. Rather than using actual human participants, we utilized an advanced deep-learning speech recognition model to simulate the effects of some important signal processing as well as psychophysical/physiological factors on speech perception. Several simulation conditions were produced by varying number of spectral bands, input frequency range, envelope cut-off frequency, envelope dynamic range and envelope quantization. Our results demonstrate that the deep-learning model exhibits human-like robustness to simulation parameters in quiet and noise, closely resembling existing human subject results. This approach is not only significantly quicker and less expensive than traditional human studies, but it also eliminates individual human variables such as attention and learning. Our findings pave the way for efficient and accurate evaluation of auditory implant simulations, aiding the future development of auditory neural prosthesis technologies.


Fc-Mediated Anomalous Biodistribution of Therapeutic Antibodies in Immunodeficient Mouse Models.
A critical benchmark in the development of antibody-based therapeutics is demonstration of efficacy in preclinical mouse models of human disease, many of which rely on immunodeficient mice. However, relatively little is known about how the biology of various immunodeficient strains impacts the in vivo fate of these drugs. Here we used immunoPET radiotracers prepared from humanized, chimeric, and murine mAbs against four therapeutic oncologic targets to interrogate their biodistribution in four different strains of immunodeficient mice bearing lung, prostate, and ovarian cancer xenografts. The immunodeficiency status of the mouse host as well as both the biological origin and glycosylation of the antibody contributed significantly to the anomalous biodistribution of therapeutic monoclonal antibodies in an Fc receptor-dependent manner. These findings may have important implications for the preclinical evaluation of Fc-containing therapeutics and highlight a clear need for biodistribution studies in the early stages of antibody drug development.Significance: Fc/FcγR-mediated immunobiology of the experimental host is a key determinant to preclinical in vivo tumor targeting and efficacy of therapeutic antibodies. Cancer Res; 78(7); 1820-32. ©2018 AACR.


Microbial nitrilases: versatile, spiral forming, industrial enzymes.
The nitrilases are enzymes that convert nitriles to the corresponding acid and ammonia. They are members of a superfamily, which includes amidases and occur in both prokaryotes and eukaryotes. The superfamily is characterized by having a homodimeric building block with a alpha beta beta alpha-alpha beta beta alpha sandwich fold and an active site containing four positionally conserved residues: cys, glu, glu and lys. Their high chemical specificity and frequent enantioselectivity makes them attractive biocatalysts for the production of fine chemicals and pharmaceutical intermediates. Nitrilases are also used in the treatment of toxic industrial effluent and cyanide remediation. The superfamily enzymes have been visualized as dimers, tetramers, hexamers, octamers, tetradecamers, octadecamers and variable length helices, but all nitrilase oligomers have the same basic dimer interface. Moreover, in the case of the octamers, tetradecamers, octadecamers and the helices, common principles of subunit association apply. While the range of industrially interesting reactions catalysed by this enzyme class continues to increase, research efforts are still hampered by the lack of a high resolution microbial nitrilase structure which can provide insights into their specificity, enantioselectivity and the mechanism of catalysis. This review provides an overview of the current progress in elucidation of structure and function in this enzyme class and emphasizes insights that may lead to further biotechnological applications.


Accidents to patients in hospital: a comparative study.
A comparative study of 50 reported accident patients (cases) and 50 non-accident patients (controls) was carried out in 10 wards in a large, acute hospital, using primary and secondary data from patients, nurses and records. Folstein's Mini-Mental State test was used to measure the mental status of patients. The mental status of the controls was significantly better than that of the cases. Nurses' responses indicated that significantly more accident patients were incontinent of urine than non-accident patients. There were also indications from patients of three additional unreported accidents. Further study was needed to estimate, more closely, the frequency of unreported patient accidents. This is the second paper in a series of three. The first appeared in Nursing Times on August 17, and the final one will be published on September 28, along with implications for practice and recommendations.


Telomeres rather than telomerase a key target for anti-cancer therapy?
It was in the 1930s that telomeres (from the Greek telos = end and meros = part) were first recognized as essential structures at the ends of the chromosomes and were shown to be important for chromosomal stability (Muller HJ: The remaking of chromosomes. The Collecting Net-Woods Hole 1938: 13: 181-198, McClintock B, The stability of broken ends of chromosomes in Zea mays. Genetics 1041: 26: 234-282). However, it was only in 1978 that the first telomeric sequence was identified -- in the protocoa Tetrahymena, a single cell organism that at a certain stage of development has many identical minichromosomes with twice as many telomeres (Blackburn EH and Gall JG. A tandemly repeated sequence at the termini of the extrachromosomal ribosomal RNA genes in Tetrahymena. J. Mol. Biol. 1978: 120: 33-53.). Today we know that telomeres form specialized, three-dimensional DNA-protein structures and fulfil important capping functions. Besides, telomeric DNA is essential as ''access DNA'' for those cells that are not able to counteract loss of DNA during replication because they do not express telomerase, the enzyme responsible for telomere length maintenance. Since telomerase is mostly found in tumor cells and inhibition correlates with telomere shortening and finally growth inhibition, telomerase and lately also the telomeres themselves have become attractive targets for anti-cancer therapy. This review aims to critically throw light on different therapeutical approaches and comes to the conclusion that telomeres may be the better targets for cancer therapeutics.


Management of histologically indolent non-Hodgkin's lymphomas.
Histologically indolent lymphomas which represent 40-50% of all non-Hodgkin's lymphomas encompass small lymphocytic lymphomas, follicular lymphomas and other entities more recently described such as mantle cell and marginal zone lymphomas. Their management has benefited from new drugs such as interferon alpha the purine analogues and new treatment modalities especially autologous stem cell transplantation.


The influence of fasudil on renal proximal tubular cell epithelial-mesenchymal transition induced by parathormone.
Renal fibrosis is a common pathway through which a variety of chronic kidney diseases progress to end-stage renal disease. Epithelial-mesenchymal transition (EMT) of renal proximal tubular cells is one of the most important factors in renal fibrosis. This study investigates if fasudil could influence EMT of renal proximal tubular cells. HK-2 cells in passage 3-4 were used for all experiments. The cells were divided into five groups and treated with different concentrations of PTH and then observe cellular morphological changes at 0, 24 and 48 h using an inverted microscope and investigate the expression of the epithelial cell marker E-cadherin and the renal fibroblast marker α-smooth muscle actin (α-SMA). PTH significantly induced EMT, fasudil-inhibited EMT induced by PTH to different degrees, and the inhibitory effect of fasudil was most pronounced at 20 μmol/L. Monitoring PTH levels, early prevention and control of hyperparathyroidism and reducing the concentration of PTH are important means to improve prognosis and delay the progression of chronic kidney disease. Fasudil can restrain EMT induced by PTH; this conclusion provides experimental data for the application of fasudil in the clinical prevention and treatment of renal fibrosis.


Traumatic Brain Injury in the Workplace.
Work-related traumatic brain injuries (TBIs) are not well documented in the literature. Published studies mostly rely on worker databases that fail to provide clinically relevant information. Our objective is to describe the characteristics of hospitalized patients and their work-related TBI. We used the Québec provincial trauma and TBI program databases to identify all patients with a diagnosis of work-related TBI admitted to the Montreal General Hospital, a level 1 trauma center, between 2000 and 2014. Data from their medical records were extracted using a predetermined information sheet. Simple descriptive statistics (means and percentages) were used to summarize the data. A total of 285 cases were analyzed. Workplace TBI patients were middle-aged (mean, 43.62 years), overwhelmingly male (male:female 18:1), mostly healthy, and had completed a high school level education. Most workers were from the construction industry; falling was the most common mechanism of injury. The majority of patients (76.8%) presented with a mild TBI; only a minority (14%) required neurosurgery. The most common finding on computed tomography was skull fracture. The median length of hospitalization was 7 days, after which most patients were discharged directly home. A total of 8.1% died of their injuries. Our study found that most hospitalized victims of work-related TBI had mild injury; however, some required neurosurgical intervention and a non-negligible proportion died of their injury. Improving fall prevention, accurately document helmet use and increasing the safety practice in the construction industry may help decrease work-related TBI burden.


Identification and partial characterization of an immunoglobulin A protease associated with human sperm.
The ability of human sperm to evade local humoral immune response at the female genital tract has received little attention. As some microorganisms inactivate secretory immunoglobulin A (S-IgA) by enzymatic degradation as a part of their pathogenic mechanism, we decided to test the hypothesis that there is an IgA protease in human semen that helps sperm to progress through the cervix uteri. Incubation of different semen fractions in the presence of S-IgA revealed IgA protease activity associated with raw semen or sperm but not with seminal plasma; raw semen and sperm produced two split products of 66 kDa and 45 kDa, respectively, in SDS-PAGE. The enzymatic activity was blocked with EDTA. IgG and IgM were not digested under the same experimental conditions. Degradation of S-IgA by an IgA protease on the sperm surface may be among the mechanisms present in semen that enable sperm to evade an immune response in the female genital tract.


Current perspectives on anaerobic infections: diagnostic approaches.
This article discusses when to look for anaerobes, anaerobic infections as clues to other problems in patients, and underlying clinical conditions as clues to the nature of anaerobic infections. Diagnostic approaches, identification methods, and susceptibility testing are reviewed.


Interaction of the membrane-bound GlnK-AmtB complex with the master regulator of nitrogen metabolism TnrA in Bacillus subtilis.
PII proteins are widespread and highly conserved signal transduction proteins occurring in bacteria, Archaea, and plants and play pivotal roles in controlling nitrogen assimilatory metabolism. This study reports on biochemical properties of the PII-homologue GlnK (originally termed NrgB) in Bacillus subtilis (BsGlnK). Like other PII proteins, the native BsGlnK protein has a trimeric structure and readily binds ATP in the absence of divalent cations, whereas 2-oxoglutarate is only weakly bound. In contrast to other PII-like proteins, Mg2+ severely affects its ATP-binding properties. BsGlnK forms a tight complex with the membrane-bound ammonium transporter AmtB (NrgA), from which it can be relieved by millimolar concentrations of ATP. Immunoprecipitation and co-localization experiments identified a novel interaction between the BsGlnK-AmtB complex and the major transcription factor of nitrogen metabolism, TnrA. In vitro in the absence of ATP, TnrA is completely tethered to membrane (AmtB)-bound GlnK, whereas in extracts from BsGlnK- or AmtB-deficient cells, TnrA is entirely soluble. The presence of 4 mm ATP leads to concomitant solubilization of BsGlnK and TnrA. This ATP-dependent membrane re-localization of TnrA by BsGlnK/AmtB may present a novel mechanism to control the global nitrogen-responsive transcription regulator TnrA in B. subtilis under certain physiological conditions.


Telangiectatic focal nodular hyperplasia of the liver: a case detected at birth.
A case of telangiectatic focal nodular hyperplasia (FNH) was detected at birth and was surgically removed. Grossly, the lesion was a solitary nodule and showed vague nodularity, appearing as an adenoma-like mass with fine fibrous septa, but having no macroscopic scar. On microscopic scale, the mass typically had neither fibrous central scar nor hyperplastic nodules different from the usual FNHs. The hepatic plates were separated by sinusoidal dilatation, sometimes alternating with areas of marked ectasia. Instead of large fibrous scar, thin fibrous septa were often found, and contained abnormal tortuous large arteries. These high-pressure vessels were connected directly into the adjacent sinusoids and made marked dilation of sinusoids. Bile ductular proliferation was also noted in the thin fibrous septa. To our knowledge, this is considered to be the first reported case of telangiectatic FNH detected at birth.


HIV Vaccine for Prevention and Cure, A Mission Possible.
HIV/AIDS was once a highly deadly infective disease that killed the global people of a million annually two decades ago. While we are enjoying the HIV therapeutic advances (mostly important from HAART invention), one obvious drawback is still unresolved-unable to clearance all HIV from infected human bodies. As a result, a series of different therapeutic attempts have been proposed based on present knowledge of different features of HIV-induced pathogenesis and human mortalities. Facing this shortcoming, innovative designs and update of HIV vaccines and other types of HIV therapeutic inventions can be a final solution for completely HIV clearance and infection managements in human beings. Owing to these scientific and medical significances, several experimental and clinical attempts have to be made. Among these attempts, part of them (updating HIV vaccine developments and clinical routines) are quite promising and noteworthy. In this article, we offer the general information of this attempt and discuss it separately, especially on the respects of HIV vaccine strategic innovations.


An application of a weak solution of the cable equation to the Rall model of a nerve cell.
The Rall model of a nerve cell with the lumped soma and natural termination boundary conditions at the nerve ends is considered as a particular case of the cable equation with oblique linear boundary conditions. A variational approach is taken to derive a weak solution of the problem. This extends classical results and removes a major obstacle of nonorthogonal boundary conditions in standard analysis of the Rall model. Additionally, new estimates of nerve cell time constants are obtained. The weak solution is applied to describe the nerve membrane potential following current injection at the soma, synaptic input, and instant unit current charge.


Evidence that insect dorsal unpaired medican (DUM) neurons are octopaminergic.
The dorsal unpaired median neuron innervating the extensor tibiae (DUMETi) of locusts and grasshoppers, as well as some other DUM neurons, cause long-term inhibition of the slow intrinsic rhythm of contraction of the muscle by releasing a neurohumoral agent. Large, (600 - 1900 A), dense-core vesicles are present in the nerve terminals. The inhibitory action is mimicked by infusioninto the leg of a minute (0.01 ml.) drop of locust saline containing a very low concentration (10(-6)M) of dopamine or noradrenaline, or an extraordinarily low concentration of octopamine (2.5 x 10(-9) M). The amplitude and frequency of the contractions slowly return to normal. Neither the cell body nor the neuron fluoresces with the Falck-Hillarp treatment, even after a period of ligature has caused an accumulation of vesicles. Octopamine does not fluoresce with this treatment. Accordingly, it is suggested that this neuron, and the other efferent DUM neurons, are octopaminergic.?23Author


Evidence implicating alpha-2 adrenergic receptors in the anticonvulsant action of intranigral muscimol.
The effects of systemically administered catecholamine receptor antagonists on the anticonvulsant action produced by local application of a gamma-aminobutyric acid agonist, muscimol, to the substantia nigra of rats were studied. Both electroshock and kindled seizures were studied. Two alpha-2 receptor antagonists, idazoxan and yohimbine, blocked the anticonvulsant action of intranigral muscimol in the electroshock model. Neither a beta nor an alpha-1 adrenergic nor a dopamine-2 receptor antagonist blocked this action. In contrast to electroshock seizures, an alpha-2 antagonist only partially reversed the anticonvulsant action of intranigral muscimol in the kindling model. We interpret the data to indicate that the interaction of norepinephrine with alpha-2 receptors is required for the anticonvulsant action of intranigral muscimol in the electroshock model. The only partial reversal found in the kindling model suggests that nigral control of seizure propagation involves more than alpha-2 receptor mediated neurotransmission.


Congenital ptosis and amblyopia.
To investigate the incidence and causes of amblyopia in congenital ptosis. The frequency and causes of amblyopia were evaluated in 83 eyes of 72 patients with congenital ptosis. Patient ages ranged between 10 months and 70 years. Amblyopia was defined as best-corrected visual acuity of 0.7 or less. After a complete ophthalmologic examination, the amount of ptosis and levator function was determined and the following amblyogenic factors were identified: ametropia, anisometropia, and strabismus. In cases with no other reason for amblyopia, stimulus deprivation amblyopia due to ptosis was assumed. The amount of ptosis was mild in 5 (6%), moderate in 26 (31%), and severe in 52 (63%) of 83 eyes with congenital ptosis. Strabismus was present in 17 (20%) eyes. Visual acuity could not be determined in 10 of 83 eyes with ptosis in children younger than 4 years. The overall incidence of amblyopia in the remaining 73 eyes was 48%. Of those patients with amblyopia, 54% had refractive errors such as anisometropia or ametropia, 20% had strabismus with or without refractive errors, and 26% had amblyopia solely attributed to ptosis. When all eyes with ptosis were included, the rate of stimulus deprivation amblyopia was 12% and all of these eyes had severe ptosis. Early detection and treatment of amblyogenic factors such as refractive errors and strabismus is recommended and, when the pupillary axis is occluded with severe ptotic eyelids, surgery should be performed as soon as possible to prevent stimulus deprivation amblyopia.


Organizing pneumonia as a possible pulmonary manifestation of systemic lupus erythematosus: Three cases and a review of literature.
Background: Organizing pneumonia (OP) is a rare manifestation of systemic lupus erythematosus (SLE). It has been described in very few case reports.Purpose and Methods: We encountered OP in three patients with SLE in 1 year; two manifested OP as an initial presentation of SLE, while the third manifested OP when SLE relapsed. To elucidate the clinical features and outcomes of OP in patients with SLE, we screened the PubMed database for cases diagnosed with OP either at or after the diagnosis of SLE; the search was restricted to articles that were published after 1990, when OP became widely recognized.Results: We identified 15 cases of OP in patients with SLE. Thus, we analyzed a total of 18 cases (including our three). OP developed at the initial diagnosis of SLE in 15 cases and at relapse of SLE in three cases. In most cases, the disease activity of SLE was moderate or high. In all cases, OP was accompanied by other extrapulmonary symptoms of SLE, namely, fever (77.8%), cutaneous manifestations (61.1%), arthralgia/arthritis (50%), and lupus nephritis (33.3%). Steroid monotherapy or increasing the dose of the steroids was effective in seven cases (38.8%); however, steroid monotherapy was ineffective and led to death due to respiratory failure in two cases (11.1%). Combination therapies of steroids with hydroxychloroquine, azathioprine, tacrolimus, mycophenolate mofetil, intravenous pulse cyclophosphamide therapy, and belimumab were effective in seven cases (38.8%).Conclusions: Based on the review of previously reported and our cases, we concluded that OP is an important pulmonary manifestation of SLE. Clinicians should be aware of it as it may require intensive immunosuppressive therapy either at or after the diagnosis of SLE.


Cyclodextrin-modified polyethylenimine polymers for gene delivery.
Linear and branched poly(ethylenimines), lPEI and bPEI, respectively, grafted with beta-cyclodextrin are prepared to give CD-lPEI and CD-bPEI, respectively, and are investigated as in vitro and in vivo nonviral gene delivery agents. The in vitro toxicity and transfection efficiency are sensitive to the level of cyclodextrin grafting. The cyclodextrin-containing polycations, when combined with adamantane-poly(ethylene glycol) (AD-PEG) conjugates, form particles that are stable at physiological salt concentrations. PEGylated CD-lPEI-based particles give in vitro gene expression equal to or greater than lPEI as measured by the percentage of EGFP expressing cells. Tail vein injections into mice of 120 microg of plasmid DNA formulated with CD-lPEI and AD-PEG do not reveal observable toxicities, and both nucleic acid accumulation and expression are observed in liver.


Trichobezoar: two case reports--a new physical sign.
Two cases of trichobezoar in young emotionally disturbed West Indian children are reported; one was due to blanket-chewing and the other was due to trichotillomania. Both were treated successfully by surgery. The previously undescribed physical sign of indentability is introduced. The literature on trichobezoars is reviewed.


NMRDyn: a program for NMR relaxation studies of protein association.
Self-association is an important biological phenomenon that is associated with many cellular processes. NMR relaxation measurements provide data about protein molecular dynamics at the atomic level and are sensitive to changes induced by self-association. Thus, measurements and analysis of NMR relaxation data can provide structurally resolved information on self-association that would not be accessible otherwise. Here, we present a computer program, NMRdyn, which analyses relaxation data to provide parameters defining protein self-association. Unlike existing relaxation analysis software, NMRdyn can explicitly model the monomer-oligomer equilibrium while fitting measured relaxation data. Additionally, the program is packaged with a user-friendly interface, which is important because relaxation data can often be large and complex. NMRdyn is available from http://research1t.imb.uq.edu.au/nmr/NMRdyn.


Time-course changes of mixture effects on AhR binding-dependent luciferase activity in a crude extract from a compost sample.
Crude extracts of environmental samples contain stable and labile aryl hydrocarbon receptor (AhR) ligands, and show huge activities in the cell-based bioassay, and these activities are higher than the chemically calculated induction equivalent values. It is thought that not only unidentified AhR ligands but also mixture effect among compounds might contribute to these activities. In the previous work, we have indicated that hydrophobic compounds in household sewage sludge (HSS) compost may interact synergistically with 2,3,7,8-TCDD in the CALUX (DR-CALUX: Dioxin-Responsive Chemical-Activated Luciferase gene eXpression) assay [Suzuki, G., Takigami, H., Kushi, Y., Sakai, S., 2004. Evaluation of mixture effects in a crude extract of compost using the CALUX bioassay and HPLC fractionation. Environ. Int. 30, 1055-1066]. In this study, we focused on co-existing stable compounds such as halogenated aromatic hydrocarbons (HAHs) and labile compounds such as polyaromatic hydrocarbons (PAHs) in the crude extract and investigated the time-course changes of mixture effects among compounds in environmental samples using the CALUX assay and normal-phase high-performance liquid chromatography (NP-HPLC) fractionation. We confirmed that CYP1A-inducing PAHs and HAHs could be separated by NP-HPLC on a nitrophenylpropylsilica (NITRO) column. To determine whether the activities of AhR ligands in environmental samples (including the HSS compost) could be assessed by the additivity theory, we compared the CALUX activity of the crude extract with the arithmetical sum of the activities of all the fractions separated by NP-HPLC. We confirmed a potentiation of CALUX activity at 12-, 24- and 48-h exposure durations. In contrast, CALUX activity increased additively at 6- and 72-h exposure durations. CALUX activity was potentiated when the CALUX activity of the HPLC fractions showed a remarkable reduction resulting in a change of activity profiles. In contrast, additivity was observed at a 72-h exposure duration when the CALUX activity of the HPLC fractions showed neither remarkable reduction nor a change in profile. Our results suggest that differences in the metabolic decomposition of compounds affected mixture effects on CALUX activity in a crude extract from HSS compost.


Cardiac sarcoma showing bone formation and neurogenic markers: report of a case.
A 54 year-old Japanese female with cardiac insufficiency was found to have a left atrial mass and smaller masses on the mitral valve. Excisional surgery of the masses and mitral valve replacement were carried out. In spite of intensive post-operative radiation therapy, the patient died of intra-atrial recurrence and brain metastases after 8 months. Tumour cells were spindled to oval, were positive for vimentin, S100 protein and neurone specific enolase. Laminin and fibronectin were also demonstrated. Bone formation and myxoid areas were present. An ultrastructurally identifiable stromal component, possibly responsible for laminin and fibronectin staining, was also present. The merits of the two main diagnostic possibilities - a mesenchymal/fibroblastic sarcoma showing bone and aberrant S100 protein, and a malignant peripheral nerve sheath tumour with bone - were discussed. In practical terms, the tumour was given the diagnosis of unclassifiable sarcoma of the left atrium. Atrial sarcomas showing neural markers and bone formation are exceedingly rare, and this report adds a further exceptionally uncommon case to the literature.


Short Term Effect of Salt Shock on Ethylene and Polyamines Depends on Plant Salt Sensitivity.
In the present manuscript the short term effect (3-24 h) of a saline shock (NaCl 100 mM) on fresh weight, water content, respiration rate, ethylene production and Na+, Cl-, ACC and polyamine concentration was studied in four plant species with different salt sensitivity, pepper, lettuce, spinach, and beetroot. Higher reduction in fresh weight and water content as a consequence of saline shock was found in pepper and lettuce plants than in spinach and beetroot, the latter behaving as more salinity tolerant. In general, salinity led to rapid increases in respiration rate, ethylene production and ACC and polyamine (putrescine, spermidine, and spermine) concentrations in shoot and root. These increases were related to plant salinity sensitivity, since they were higher in the most sensitive species and vice versa. However, ethylene and respiration rates in salt stressed plants recovered similar values to controls after 24 h of treatment in salt tolerant plants, while still remaining high in the most sensitive. On the other hand, sudden increases in putrescine, spermidine, and spermine concentration were higher and occurred earlier in pepper and lettuce, the most sensitive species, than in spinach and beetroot, the less sensitive ones. These increases tended to disappear after 24 h, except in lettuce. These changes would support the conclusion that ethylene and polyamine increases could be considered as a plant response to saline shock and related to the plant species sensitivity to this stress. In addition, no competition between polyamines and ethylene biosynthesis for their common precursor was observed.


Liquid Crystal-Infused Porous Polymer Surfaces: A "Slippery" Soft Material Platform for the Naked-Eye Detection and Discrimination of Amphiphilic Species.
We report the design and characterization of liquid crystal (LC)-infused porous polymer membranes that can detect and report on the presence of natural and synthetic amphiphiles in aqueous solution. We demonstrate that thermotropic LCs can be infused into nanoporous polymer membranes to yield LC-infused surfaces that exhibit slippery behaviors in contact with a range of aqueous fluids. In contrast to conventional liquid-infused surfaces (LIS) or slippery liquid-infused porous surfaces (SLIPS) prepared using isotropic oils, aqueous solutions slide over the surfaces of these LC-infused materials at speeds that depend strongly upon the composition of the fluid, including the presence, concentration, or structure of a dissolved surfactant. In general, the sliding times of aqueous droplets on these LC-infused surfaces increase significantly (e.g., from times on the order of seconds to times on the order of minutes) with increasing amphiphile concentration, allowing sliding times to be used to estimate the concentration of the amphiphile. Additional experiments revealed other intrinsic and extrinsic variables or parameters that can be used to further manipulate droplet sliding times and discriminate among amphiphiles of similar structure. Our results are consistent with a physical picture that involves reversible changes in the interfacial orientation of anisotropic LCs mediated by the interfacial adsorption of amphiphiles. These materials thus permit facile "naked-eye" detection and discrimination of amphiphiles in aqueous samples using equipment no more sophisticated than a stopwatch. We demonstrate the potential utility of these LC-infused surfaces for the unaided, naked-eye detection and monitoring of amphiphilic biotoxins in small droplets of fluid extracted directly from cultures of two common bacterial pathogens (Pseudomonas aeruginosa and Staphylococcus aureus). The ability to translate molecular interactions at aqueous/LC interfaces into large and readily observed changes in the sliding times of small aqueous droplets on surfaces could open the door to new applications for antifouling, liquid-infused materials in the context of environmental sensing and other fundamental and applied areas.


Satellite glia activation in dorsal root ganglion contributes to mechanical allodynia after selective motor fiber injury in adult rats.
Increasing evidence suggests that activation of satellite glia cells (SGCs) in sensory ganglia play important roles in the development of neuropathic pain. The present study aimed to investigate the involvement of SGC activation in a novel model of motor nerve injury induced pain hypersensitivity. The neuropathic pain model was established by cervical 8 ventral root avulsion (C8VA). Glial fibrillary acidic protein (GFAP) was used as a marker of SGC activation. Unilateral C8VA resulted in mechanical allodynia, but not thermal hyperalgesia in bilateral paws. Expectedly, SGCs were robustly activated on as early as 1 day and persisted for at least 7 days in the ipsilateral and contralateral dorsal root ganglia (DRG) of C6, C7 and C8 after C8VA. Double immunofluorescence showed that almost all the activated SGCs enveloped neurofilament 200 (NF200) positive myelinated neurons in DRG. Local application of fluorocitrate (FC), a glial metabolism inhibitor, significantly decreased the number of activated SGCs and alleviated bilateral mechanical allodynia. These results suggest that SGC activation contributed to ipsilateral and mirror-image pain hypersensitivity after C8VA. Inhibition of SGC activation represented a promising therapeutic strategy for the management of neuropathic pain following brachial plexus root avulsion.


Sinusitis and asthma: clinical and pathogenetic relationships.
Sinusitis has been considered to be a possible causal factor for asthma. Reflex has also been postulated between the upper and lower airway. Data for and against the existence of such a reflex are presented, together with the diagnosis and management of sinusitis.


Emerging contaminants of high concern and their enzyme-assisted biodegradation - A review.
The widespread occurrence and adverse environmental and health-related impacts of various types of emerging contaminants (ECs) have become an issue of high concern. With ever increasing scientific knowledge, socio-economic awareness, health-related problems and ecological apprehensions, people are more concerned about the widespread ECs, around the globe. Among ECs, biologically active compounds from pharmaceutical, cosmeceutical, biomedical, personal care products (PPCPs), endocrine-disrupting chemicals (EDCs), and flame-retardants are of paramount concern. The presence and persistence of ECs in water bodies are of continued and burning interest, worldwide. Various types of ECs are being discharged knowingly/unknowingly with/without partial treatments into the aquatic environments that pose serious health issues and affects the entire living ecosystem. So far, various approaches have been developed for ECs degradation and removal to diminish their adverse impact. Many previous and/or ongoing studies have focused on contaminants degradation and efficient removal via numerous treatment strategies, i.e. (1) physical, (2) chemical and (3) biological. However, the experimental evidence is lacking to enable specific predictions about ECs mechanistic degradation and removal fate across various in-practice systems. In this context, the deployment oxidoreductases such as peroxidases (lignin peroxidases, manganese-dependent peroxidases, and horseradish peroxidase), aromatic dioxygenases, various oxygenases, laccases, and tyrosinases have received considerable research attention. Immobilization is highlighted as a promising approach to improve enzyme catalytic performance and stabilization, as well as, to protect the three-dimensional structure of the enzyme against the undesirable consequences of harsh reaction environment. This work overviews the current and state-of-the-art critical aspect related to hazardous pollutants at large and ECs in particular by the immobilized oxidoreductase enzymes. The first part of the review focuses on the occurrence, physiochemical behavior, potent sources and significant routes of ECs. Following that, environmentally-related adverse impacts and health-related issues of ECs are discussed in the second part. In the third part, biodegradation and removal strategies with a comparative overview of several conventional vs. non-conventional methods are presented briefly. The fourth part majorly focuses on operational modes of different oxidoreductase enzyme-based biocatalytic processes for the biodegradation and biotransformation of a wide array of harmful environmental contaminants. Finally, the left behind research gaps, concluding remarks as well as future trends and recommendations in the use of carrier-immobilized oxidoreductases for environmental perspective are also discussed.


Long-term Follow-up of Revision Osteochondral Allograft Transplantation of the Ankle.
Osteochondral allograft (OCA) transplantation is a useful alternative for treatment of posttraumatic ankle arthritis in young patients but has a relatively high failure rate and further procedures are often required. The purpose of this study was to evaluate outcomes of patients who underwent revision OCA transplantation of the ankle after failed primary OCA transplantation. Twenty patients underwent revision OCA transplantation of the ankle between 1988 and 2015. Mean age was 44 years, 55% (11 of 20) were female. The mean time from primary to revision OCA was 3.0 ± 1.7 years. All patients had a minimum follow-up of 2 years. Outcomes included the American Academy of Orthopaedic Surgeons Foot and Ankle Module (AAOS-FAM) and questionnaires evaluating pain and satisfaction. Failure of the revision OCA was defined as a conversion to arthroplasty, arthrodesis, or amputation. Ten of 20 ankles required further surgery, of which 30% (6 of 20) were considered OCA revision failures (4 arthrodeses, 1 arthroplasty, and 1 amputation). The mean time to failure was 6.7 (range, 0.6-13.1) years. Survivorship of the revision OCA was 84% at 5 years and 65% at 10 years. The 14 patients with grafts remaining in situ had an average follow-up of 10.3 years; mean AAOS-FAM Core Score was 70.5 (range, 42.3-99). Of the patients who answered the follow-up questions, 4 of 7 reported moderate to severe pain, and 5 of 12 were satisfied with the results of the procedure. Although the results of revision ankle OCA transplantation are not inferior to primary OCA transplantation, the high rates of persistent pain, further surgery, and graft failure suggest that the indications for OCA as a revision procedure should be carefully evaluated, with proper patient selection. Considering the treatment alternatives, revising a failed OCA transplantation can be a useful treatment option, especially for young and active patients who wish to avoid arthrodesis or arthroplasty. Level IV, case series.


Hydrogen Sulfide and Glucose Homeostasis: A Tale of Sweet and the Stink.
Among many endogenous mediators, the gasotransmitter hydrogen sulfide (H2S) plays an important role in the regulation of glucose homeostasis. In this article we discuss different functional roles of H2S in several metabolic organs/tissues required in the maintenance of glucose homeostasis. Recent Advances: New evidence has emerged revealing the insulin sensitizing role of H2S in adipose tissue and skeletal muscle biology. In addition, H2S was demonstrated to be a potent stimulator of gluconeogenesis via the induction and stimulation of various glucose-producing pathways in the liver. Similar to its other physiological effects, H2S exhibits paradoxical characteristics in the regulation of glucose homeostasis: (1) H2S stimulates glucose production via activation of gluconeogenesis and glycogenolysis in hepatocytes, yet inhibits lipolysis in adipocytes; (2) H2S stimulates glucose uptake into adipocytes and skeletal muscle but inhibits glucose uptake into hepatocytes; (3) H2S inhibits insulin secretion from pancreatic β cells, yet sensitizes insulin signaling and insulin-triggered response in adipose tissues and skeletal muscle. It is also unclear the impact H2S may have on glucose metabolism and utilization by other vital organs, such as the brain. Recent reports and ongoing studies lay the foundation for a general, although highly incomplete, understanding of the effect of H2S on regulating glucose homeostasis. In this review, we describe the molecular mechanisms and physiological outcomes of the gasotransmitter H2S on organs and tissues required for homeostatic maintenance of blood glucose. Future directions highlighting the H2S-mediated homeostatic control of glucose metabolism under physiological and insulin-resistant conditions are also discussed. Antioxid. Redox Signal. 28, 1463-1482.


Profile of Endothelin-1, Nitric Oxide, and Prostacyclin Levels in Pulmonary Arterial Hypertension Related to Uncorrected Atrial Septal Defect: Results from a Single Center Study in Indonesia.
The study design was cross-sectional. The subjects were adult uncorrected secundum ASD with PAH. Pulmonary artery pressure was measured with right heart catheterization. Pulmonary venous blood was obtained during catheterization for measuring endothelin-1, prostacyclin, and nitric oxide. Correlation tests were performed to determine any association between biomarkers and mean pulmonary artery pressure (mPAP). The levels of biomarkers were compared based on the severity of PAH. Statistical significance was determined at p < 0.05. Forty-four subjects were enrolled in this study. Endothelin-1 level and mPAP had significant moderate positive correlation (r = 0.423 and p value = 0.004). However, no significant correlation was observed between prostacyclin, nitric oxide levels, and mPAP. The pattern of endothelin-1, prostacyclin, and nitric oxide was distinctive. Levels of endothelin-1 were incrementally increased from mild, moderate, to severe PAH. The levels of prostacyclin and nitric oxide had similar pattern in association with the severity of PAH, which was increased in mild-to-moderate PAH but decreased in severe PAH. There was a distinctive pattern of endothelin-1, prostacyclin, and nitric oxide based on severity of PAH in adult uncorrected ASD. Significant correlations existed between endothelin-1 and the severity of PAH and mPAP.


Phase II trial of bevacizumab and everolimus in patients with advanced renal cell carcinoma.
To evaluate the efficacy and toxicity of the combination of bevacizumab, an angiogenesis inhibitor, and everolimus, an mTOR inhibitor, in the treatment of patients with advanced clear cell renal carcinoma. Two groups of patients with metastatic renal cell carcinoma were eligible for this study: those with no previous treatment with targeted agents and those with previous treatment with sunitinib and/or sorafenib. All patients received bevacizumab 10 mg/kg intravenously every 2 weeks and everolimus 10 mg orally daily. Patients were evaluated for response after 8 weeks of treatment; patients with objective response or stable disease continued treatment until disease progression or unacceptable toxicity occurred. Eighty patients (50 untreated, 30 previously treated) entered this clinical trial. The combination of bevacizumab/everolimus showed activity in both groups. Median progression-free survivals in previously untreated and previously treated patients were 9.1 and 7.1 months, respectively. Overall response rates (30% and 23%) were similar in both groups. The regimen was well tolerated by most patients, with a toxicity profile as expected based on the known toxicities of these two agents. Grade 3 to 4 proteinuria was more frequent than expected (25%) and led to treatment discontinuation in six patients. Bevacizumab/everolimus is active and well tolerated in the treatment of advanced clear cell renal cancer, either as first-line treatment or after treatment with sunitinib and/or sorafenib. The benefits of this combination regimen, versus sequential use of these two agents, requires further study.


Effect of electroacupuncture at Sibai on the gastric myoelectric activities of denervated rats.
To explore the mechanism of the exciting effects of electro-acupuncture (EA) at Sibai on the gastric myoelectric activities. A total of 32 rats were randomly divided into four groups. Through intraperitoneal injection with atropine (the anti-cholinergic agent by blockade of muscarinic receptors), hexamethonium (automatic nerve ganglion-blocking agent) and reserpine (anti-adrenergic agent by depleting the adrenergic nerve terminal of its norepinephrine store), effects of EA at Sibai on the gastric myoelectric activities of the denervated rats were observed. After intraperitoneal injection of atropine and hexamethonium, the average amplitude and ratio of period to time in the phase of high activity of gastric myoelectric slow wave, and the average numbers of the peaks of gastric myoelectric fast wave were significantly decreased (P<0.01, P<0.05, P<0.01), while after intraperitoneal injection of reserpine, the aforementioned three parameters were increased (P<0.01, P<0.05, P<0.01). EA at Sibai point partially relieved the inhibitory effect of atropine and hexamethonium on the gastric myoelectric activities in the rats (P<0.05 or P>0.05). Cholinergic and adrenergic nervous systems and autonomic nerve ganglion participate in the peripheral passage of the controlling effects of EA at Foot Yangming Channel on gastrointestinal tract.


Development and validation of Visual Impairment as a Risk for Falls Questionnaire.
visual impairment is associated with an increased risk of falls, yet eye care professionals are infrequently members of falls prevention clinics. The aim of this preliminary study was to validate a newly created Visual Impairment as a Risk for Falls Questionnaire intended to be used by those professionals not involved in eye care. about 53 participants with various visual impairments known to be associated with falls and 33 participants with normal sight were contacted within 4 months of a full oculo-visual assessment and were asked the questions from the current questionnaire pertaining to their visual function. A retrospective file review was undertaken and the sensitivity and specificity of participants' responses were calculated compared to the actual vision impairment based on the findings from their visual assessment. the question regarding ability to read was included to identify people with central vision loss, a risk factor for falling. It was found to have sensitivity of 74% and specificity of 87%. Both sensitivity and specificity improved when participants with cognitive impairment were excluded. The question on recognising facial features gave sensitivity of 73% and specificity of 97% for this subgroup. However, questions related to impairments in stereopsis and peripheral fields were not useful. the study demonstrates that several questions of the new questionnaire are useful; however, further testing with a larger population is needed to fully validate the questionnaire for use by health care professionals.


Glyma11g13220, a homolog of the vernalization pathway gene VERNALIZATION 1 from soybean [Glycine max (L.) Merr.], promotes flowering in Arabidopsis thaliana.
The precise timing of flowering is fundamental to successful reproduction, and has dramatic significance for crop yields. Although prolonged low temperatures are not required for flowering induction in soybean, vernalization pathway genes have been retained during the evolution of this species. Little information is currently available in regarding these genes in soybean. We were able to detect the expression of Glyma11g13220 in different organs at all monitored developmental stages in soybean. Glyma11g13220 expression was higher in leaves and pods than in shoot apexes and stems. In addition, Glyma11g13220 was responsive to photoperiod and low temperature in soybean. Furthermore, Glyma11g13220 was found to be a nuclear-localized protein. Over-expression of Glyma11g13220 in an Arabidopsis Columbia-0 (Col-0) background resulted in early flowering. Quantitative real-time PCR analysis revealed that transcript levels of flower repressor FLOWERING LOCUS C (FLC), and FD decreased significantly in transgenic Arabidopsis compared with wild-type Col-0, while the expression of VERNALIZATION INSENSITIVE 3 (VIN3) and FLOWERING LOCUS T (FT) noticeably increased. Our results suggest that Glyma11g13220, a homolog of Arabidopsis VRN1, is a functional protein. Glyma11g13220, which is responsive to photoperiod and low temperature in soybean, may participate in the vernalization pathway in Arabidopsis and help regulate flowering time. Arabidopsis VRN1 and Glyma11g13220 exhibit conserved as well as diverged functions.


Novel models for RNA splicing that involve a small nuclear RNA.
Nucleotide sequences of mammalian small nuclear RNAs (snRNAs) have been analyzed with a computer program for complementarity with sequences around a splice junction of various eukaryotic mRNA precursors (pre-mRNAs). A region in U2 RNA or some other snRNAs can form base pairs with both exons surrounding an intron of certain pre-mRNAs and, thereby, can align the two junctions leading to correct splicing of the pre-mRNA. These findings suggest that a snRNA such as U2 can be involved in splicing certain pre-mRNAs by pairing with exons, which we we call an "exon model" for splicing, as compared with the model involving U1 RNA presented by Lerner et al. [Lerner, M. R., Boyle, J. A., Mount, S. M., Wolin, S. L. & Steitz, J. A. (1980) Nature (London) 283, 220-224]. We constructed a secondary structure model of U1 RNA and studied the capacity of base pairing with pre-mRNAs on the basis of both primary and secondary structures of U1 RNA. We present an alternative model for splicing that involves U1 RNA, which assumes base pairing of noncontiguous regions of U1 RNA with an intron of a pre-mRNA. Pairing of an snRNA with exons could explain correct matching of the two junctions that bound one and the same intron, which is not explained by pairing with consensus sequences at the ends of an intron as proposed by Lerner et al. Pairing of an intron with U1 RNA and pairing of the surrounding exons with another snRNA such as U2 RNA could take place at the same time to insure specificity of splicing.


Asthma and obesity in adolescents: is there an association?
To determine if obesity is more prevalent in adolescents with asthma compared with nonasthmatic adolescents and to determine if obesity is associated with more severe asthma, we studied 265 adolescent asthmatics 12-21 years of age and 482 nonasthmatic adolescents. The prevalence of obesity in the asthmatic group was 20% compared to 17% in the control group. The prevalence of being at risk of overweight was similar for asthmatics (16%) and controls (15%). The prevalence of obesity in moderate to severe asthmatics (21%) was not different from prevalence of obesity in mild asthmatics (19%) or controls (17%). In this study of primarily African-American urban adolescents, obesity was not associated with asthma or more severe asthma.


Orai and TRPC channel characterization in FcεRI-mediated calcium signaling and mediator secretion in human mast cells.
Inappropriate activation of mast cells via the FcεRI receptor leads to the release of inflammatory mediators and symptoms of allergic disease. Calcium influx is a critical regulator of mast cell signaling and is required for exocytosis of preformed mediators and for synthesis of eicosanoids, cytokines and chemokines. Studies in rodent and human mast cells have identified Orai calcium channels as key contributors to FcεRI-initiated mediator release. However, until now the role of TRPC calcium channels in FcεRI-mediated human mast cell signaling has not been published. Here, we show evidence for the expression of Orai 1,2, and 3 and TRPC1 and 6 in primary human lung mast cells and the LAD2 human mast cell line but, we only find evidence of functional contribution of Orai and not TRPC channels to FcεRI-mediated calcium entry. Calcium imaging experiments, utilizing an Orai selective antagonist (Synta66) showed the contribution of Orai to FcεRI-mediated signaling in human mast cells. Although, the use of a TRPC3/6 selective antagonist and agonist (GSK-3503A and GSK-2934A, respectively) did not reveal evidence for TRPC6 contribution to FcεRI-mediated calcium signaling in human mast cells. Similarly, inactivation of STIM1-regulated TRPC1 in human mast cells (as tested by transfecting cells with STIM1-KK684-685EE - TRPC1 gating mutant) failed to alter FcεRI-mediated calcium signaling in LAD2 human mast cells. Mediator release assays confirm that FcεRI-mediated calcium influx through Orai is necessary for histamine and TNFα release but is differentially involved in the generation of cytokines and eicosanoids.


Interventions by critical care nurses reduce VAP.
Critically ill patients who have been mechanically ventilated longer than 48 hours are at increased risk for developing ventilator-associated pneumonia, a nosocomial infection that is the leading cause of morbidity and mortality in the intensive care unit. In this article, the care provided by critical care nurses to reduce the risk of this potentially lethal complication is discussed.


The fitness consequences of wildlife conservation translocations: a meta-analysis.
Conservation translocation is a common strategy to offset mounting rates of population declines through the transfer of captive- or wild-origin organisms into areas where conspecific populations are imperilled or completely extirpated. Translocations that supplement existing populations are referred to as reinforcements and can be conducted using captive-origin animals [ex situ reinforcement (ESR)] or wild-origin animals without any captive ancestry [in situ reinforcement (ISR)]. These programs have been criticized for low success rates and husbandry practices that produce individuals with genetic and performance deficits, but the post-release performance of captive-origin or wild-origin translocated groups has not been systematically reviewed to quantify success relative to wild-resident control groups. To assess the disparity in post-release performance of translocated organisms relative to wild-resident conspecifics and examine the association of performance disparity with organismal and methodological factors across studies, we conducted a systematic review and meta-analysis of 821 performance comparisons from 171 studies representing nine animal classes (101 species). We found that translocated organisms have 64% decreased odds of out-performing their wild-resident counterparts, supporting claims of systemic issues hampering conservation translocations. To help identify translocation practices that could maximize program success in the future, we further quantified the impact of broad organismal and methodological factors on the disparity between translocated and wild-resident conspecific performance. Pre-release animal enrichment significantly reduced performance disparities, whereas our results suggest no overall effects of taxonomic group, sex, captive generation time, or the type of fitness surrogate measured. This work is the most comprehensive systematic review to date of animal conservation translocations in which wild conspecifics were used as comparators, thereby facilitating an evaluation of the overall impact of this conservation strategy and identifying specific actions to increase success. Our review highlights the need for conservation managers to include both sympatric and allopatric wild-reference groups to ensure the post-release performance of translocated animals can be evaluated. Further, our analyses identify pre-release animal enrichment as a particular strategy for improving the outcomes of animal conservation translocations, and demonstrate how meta-analysis can be used to identify implementation choices that maximize translocated animal contributions to recipient population growth and viability.


Protective effects of probiotics against tannin-induced immunosuppression in broiler chickens.
Tannins (TAs) are an anti-nutritional substance commonly used as a natural feed additive for livestock. However, our previous study described the dose-dependent adverse effects of TA on immune responses and growth in chickens. In this study, we evaluated the protective effects of a probiotic preparation (BT) consisting of three different bacteria (Bacillus mesenteric, Clostridium butyricum, and Streptococcus faecalis) against TA-induced immunosuppression in chickens. Forty chicks were divided into 4 groups as follows: the CON group (basal diet), BT group supplemented with 3 g BT/kg diet, tannic acid (TA) group supplemented with 30 g TA/kg diet, and BT+TA group supplemented with 3 g BT/kg diet + 30 g TA/kg diet. The feeding trial lasted for 35 days. Lymphocyte subset, macrophage phagocytosis, cytokine mRNA expression, and primary and secondary IgY immune responses were evaluated. BT supplementation significantly improved TA-induced reductions in final body weight, body weight gain, feed intake, and relative weights of lymphoid organs compared with the TA group. Furthermore, in the spleen and cecal tonsil (CT), the relative populations of CD4+, CD8+, and CD4+CD8+ cells in the BT+TA group were significantly ameliorated compared with the TA group. Additionally, comparison with the TA group showed that the chickens in the BT+TA group had an improved relative population of B cells in the CT and that macrophage phagocytosis in the spleen was significantly increased. Chickens in the BT+TA group showed significant increases in IFN-γ and IL-4 mRNA expression in the spleen compared with the TA group. The primary and secondary IgY responses were significantly improved. These results revealed that supplementation with BT protects against TA-induced immunosuppression in chickens.